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Biomedical subjects

P J Rice

Publications and source records attributed to P J Rice.

At least 19 recordsLinked to original sources
PubMed2006

Paranodal pathology in Tangier disease with remitting-relapsing multifocal neuropathy.

Pathological studies of a sural nerve biopsy in a man with Tangier disease presenting as a remitting-relapsing multifocal neuropathy showed abnormalities in the paranodal regions, including lipid deposition (65%) and redundant myelin foldings, with various degrees of myelin splitting and vesiculation (43%) forming small tomacula and abnormal myelin terminal loops (4%). The internodal regions were normal in the majority of myelinated fibres. Abnormal lipid storage was also present in the Schwann cells of the majority of unmyelinated fibres (67%). The evidence suggests that the noncompacted myelin region of the paranode is a preferential site for lipid storage in the myelinated Schwann cell, and that the space-occupying effects of the cholesterol esters leads to paranodal malfunction and tomacula formation as the pathological basis for the multifocal relapsing-remitting clinical course.

Adolescent↗
PubMed2001

The importance of a beta-glucan receptor in the nonopsonic entry of nontypeable Haemophilus influenzae into human monocytic and epithelial cells.

Previous reports showed that nontypeable Haemophilus influenzae (NTHi) reside in macrophage-like cells in human adenoid tissue. This study investigated the ability of nonopsonized NTHi and encapsulated H. influenzae type b (Hib) to enter human monocytic and epithelial cells. The number of intracellular bacteria was determined by a viability assay and flow cytometry. To characterize the mechanisms responsible for the internalization of NTHi, different inhibitors of surface molecules, receptor turnover, and the cytoskeleton were used. Hib were found in monocytic cells at very low numbers (<100 bacteria/2x105 cells). In contrast, a great variation in intracellular numbers was detected between the different NTHi isolates (range, 0.0007%-0.28% of the inoculum for monocytes and 0.053%-3.5% for epithelial cells). NTHi entered human monocytic and epithelial cells via a receptor-mediated endocytosis involving mainly a beta-glucan receptor that could be blocked by laminarin.

Carcinoma↗
PubMed2001

Normal human fibroblasts express pattern recognition receptors for fungal (1-->3)-beta-D-glucans.

Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity. Glucans are thought to mediate their effects via interaction with membrane receptors on macrophages, neutrophils, and NK cells. There have been no reports of glucan receptors on nonimmune cells. We investigated the binding of a water-soluble glucan in primary cultures of normal human dermal fibroblasts (NHDF). Membranes from NHDF exhibited saturable binding with an apparent dissociation constant (K(D)) of 8.9 +/- 1.9 microg of protein per ml and a maximum binding of 100 +/- 8 resonance units. Competition studies demonstrated the presence of at least two glucan binding sites on NHDF. Glucan phosphate competed for all binding sites, with a K(D) of 5.6 microM (95% confidence interval [CI], 3.0 to 11 microM), while laminarin competed for 69% +/- 6% of binding sites, with a K(D) of 3.7 microM (95% CI, 1.9 to 7.3 microM). Glucan (1 microg/ml) stimulated fibroblast NF-kappaB nuclear binding activity and interleukin 6 (IL-6) gene expression in a time-dependent manner. NF-kappaB was activated at 4, 8, and 12 h, while IL-6 mRNA levels were increased by 48% at 8 h. This is the first report of pattern recognition receptors for glucan on human fibroblasts and the first demonstration of glucan binding sites on cells other than leukocytes. It also provides the first evidence that glucans can directly modulate the functional activity of NHDF. These results provide new insights into the mechanisms by which the host recognizes and responds to fungal (1-->3)-beta-D-glucans and suggests that the response to glucans may not be confined to cells of the immune system.

Binding Sites↗
PubMed2000

The influence of glucan polymer structure and solution conformation on binding to (1-->3)-beta-D-glucan receptors in a human monocyte-like cell line.

Glucans are (1-3)-beta-D-linked polymers of glucose that are produced as fungal cell wall constituents and are also released into the extracellular milieu. Glucans modulate immune function via macrophage participation. The first step in macrophage activation by (1-3)-beta-D-glucans is thought to be the binding of the polymer to specific macrophage receptors. We examined the binding/uptake of a variety of water soluble (1-3)-beta-D-glucans and control polymers with different physicochemical properties to investigate the relationship between polymer structure and receptor binding in the CR3- human promonocytic cell line, U937. We observed that the U937 receptors were specific for (1-->3)-beta-D-glucan binding, since mannan, dextran, or barley glucan did not bind. Scleroglucan exhibited the highest binding affinity with an IC(50)of 23 nM, three orders of magnitude greater than the other (1-->3)-beta-D-glucan polymers examined. The rank order competitive binding affinities for the glucan polymers were scleroglucan>>>schizophyllan > laminarin > glucan phosphate > glucan sulfate. Scleroglucan also exhibited a triple helical solution structure (nu = 1.82, beta = 0.8). There were two different binding/uptake sites on U937 cells. Glucan phosphate and schizophyllan interacted nonselectively with the two sites. Scleroglucan and glucan sulfate interacted preferentially with one site, while laminarin interacted preferentially with the other site. These data indicate that U937 cells have at least two non-CR3 receptor(s) which specifically interact with (1-->3)-beta-D-glucans and that the triple helical solution conformation, molecular weight and charge of the glucan polymer may be important determinants in receptor ligand interaction.

Animals↗
PubMed1999

cAMP and in vitro inotropic actions of secretin and VIP in rat papillary muscle.

Secretin and VIP stimulate cardiac adenylyl cyclase activity and exert a positive inotropic action in several mammalian species. This study examined positive inotropic activity and cAMP levels in rat papillary muscle. Isoproterenol and secretin increased contractions by 150+/-31% and 129+/-27%, respectively. VIP increased contraction by 30+/-21% only at 10 microM. Isoproterenol significantly increased cAMP levels by 82%, whereas increases by secretin (58%) and VIP (56%) were not significant. These results are consistent with reports that secretin and VIP stimulate cardiac adenylyl cyclase in the rat, but suggest that cAMP tissue levels cannot totally explain the positive inotropic responses to secretin and VIP.

Animals↗
PubMed1998

Relaxation of isolated human myometrial muscle by beta2-adrenergic receptors but not beta1-adrenergic receptors.

OBJECTIVE: Human myometrium contains both beta1-adrenergic and beta2-adrenergic receptors. This study was designed to assess the importance of each beta-adrenergic receptor subtype in relaxation of human myometrial muscle strips. STUDY DESIGN: Radioligand binding studies were used to establish the presence of each beta-adrenergic receptor subtype, whereas highly selective beta1-antagonists and beta2-antagonists were used to assess the contribution of beta-adrenergic receptor subtypes to myometrial relaxation after exposure to (-)-isoproterenol. RESULTS: Membranes prepared from myometrium contained 82% +/- 4% beta2-adrenergic receptors. After contraction produced by exposure to potassium chloride (35 mmol/L), isoproterenol produced relaxation with half maximal effect at 0.02 micromol/L and a maximal relaxation of 52% +/- 3%. Beta1-antagonist CGP-20712A had no significant effect, whereas beta2-antagonist ICI-118551 produced a characteristic rightward shift of the isoproterenol concentration-relaxation relationship. CONCLUSIONS: Although both beta1-adrenergic receptors and beta2-adrenergic receptors are present in human myometrial tissue at term, relaxation by nonselective beta-agonist isoproterenol is mediated exclusively by beta2-adrenergic receptors.

Adrenergic beta-Agonists↗
PubMed1997

Extraneuronal uptake inhibitor U-0521 decreases contractile responses in rat vas deferens.

1. The influence of catechol-O-methyltransferase inhibitor U-0521 on isotonic contraction of isolated rat vas deferens was examined to determine optimal concentration and nonspecific effects. 2. Maximum responses to (-)-epinephrine were increased at 0.4 microM and 1 microM concentrations of U-0521. Epinephrine responses were progressively decreased in the presence of higher concentrations (10 microM, 30 microM and 100 microM) of U-0521. 3. The response to the nonadrenergic agonist neurokinin A was similarly depressed in the presence of 100 microM U-0521. 4. U-0521 not only inhibits COMT, at concentrations above 1 microM it nonspecifically depresses contraction of the rat vas deferens by both adrenergic and nonadrenergic agonists.

Adrenergic alpha-Agonists↗
PubMed1997

von Willebrand factor and factor VIII: C in acute cerebrovascular disease. Relationship to stroke subtype and mortality.

BACKGROUND: Elevated von Willebrand factor (vWF) is a risk factor in the development of acute myocardial infarction. The importance of vWF and factor VII:C in the pathogenesis of cerebrovascular disease (CVD) is poorly defined. METHODS AND RESULTS: We studied 208 cases of stroke whose pathological type was defined by cranial computed tomography. Cerebral infarcts were grouped according to the Oxfordshire Community Stroke Project (OCSP) clinical classification. The results in patients were compared with 184 healthy reference subjects. In patients, vWF and FVIII:C levels were determined initially and after three months. Patients were followed prospectively for six months or until death. Levels of vWF and FVIII:C were elevated initially (1.86 IU/ml and 2.20 U/ml respectively) and after 3 months (1.51 IU/ml and 1.90 U/ml) compared with a healthy reference population (1.26 IU/ml and 1.49 U/ml p = 0.0001). In the initial sample, vWF was associated with age (p = 0.01). FVIII:C was related to age (p = 0.04), gender (p = 0.007 higher for females) and a history of diabetes mellitus (2.56 U/ml vs. 2.16 U/ml in non-diabetics, p = 0.008). Initial vWF levels were higher in subjects with large vessel disease (TACI/PACI) group compared with the small vessel disease (LACI) group [2.12 IU/ml, (n = 112) vs. 1.48 IU/ml (n = 59) respectively, p = 0.0001] and similarly in initial FVIII:C levels (2.43 U/ml vs. 1.87 U/ml, p = 0.0001). Analysis of six-month case fatality, vWF levels were associated with risk of death [p = 0.01, OR 1.73 (1.12, 2.66) for an increase of I U/ml], even after allowing for stroke type. CONCLUSION: The relationship of vWF with stroke mortality has not previously been described. Although we have not demonstrated a causal role for vWF in the pathogenesis of CVD, elevated circulating levels of vWF may be associated with increased risk of death following stroke. A prospective study would be required to establish whether vWF is predictive for the development of CVD.

Acute Disease↗
PubMed1996

Receptor binding and internalization of a water-soluble (1-->3)-beta-D-glucan biologic response modifier in two monocyte/macrophage cell lines.

Glucan phosphate, a water-soluble, chemically defined (1-->3)-beta-D-glucan biologic response modifier, has been reported to exert antisepsis activity and accelerate wound healing. In this study we describe the specific binding of glucan phosphate to human and murine monocyte/macrophage cell lines, U937 and J774A.1, respectively. At 37 degrees C, equilibrium binding was rapidly achieved, i.e., within 1 min. In U937 cells, binding occurred with an affinity (Kd) of 37 microM and a Bmax of 65 x 106 binding sites/cell at 37 degrees C. In J774A.1 cells, glucan phosphate bound with an affinity (Kd) of 24 microM and a Bmax of 53 x 106 binding sites/cell at 37 degrees C. In both cases there was insignificant nonspecific binding. We further demonstrated that bound glucan phosphate cannot be displaced by a 50-fold excess of unlabeled ligand, suggesting internalization of glucan phosphate. Transmission electron microscopy showed significantly increased cytoplasmic vacuolization and significantly decreased mitotic activity in glucan phosphate-treated U937 cells compared with that in untreated cells. Pullulan, a random coil alpha-(1-->4)-(1-->6)-linked glucose polymer that served as a control, did not compete for the same binding site as glucan phosphate in either cell line, indicating the specificity of the binding site for (1-->3)-beta-D-glucans. We conclude that water-soluble pharmaceutical grade (1-->3)-beta-D-glucan phosphate specifically binds to and is internalized by U937 and J774A.1 cells.

Animals↗
PubMed1996

Concentration-response relationships for adenosine agonists during preconditioning of rabbit cardiomyocytes.

Although adenosine receptors have been implicated in the induction of preconditioning in a variety of experimental models, there is controversy concerning the specific adenosine receptor subtypes mediating this effect. Concentration-protection relationships for adenosine and adenosine agonists in rabbit cardiomyocytes were used to characterize the role of adenosine receptor subtypes in preconditioning. Isolated cells were ischemically preconditioned or pre-incubated for 10 min with increasing concentrations of adenosine, CCPA (2-chloro-N6-cyclopentyladenosine), APNEA (N6-2-(4-aminophenyl)ethyladenosine), or BNECA (N6-benzyl-5'-N-ethyl-carboxamidoadenosine) in the presence or absence of 1 or 10 microM of the selective A1-adenosine antagonist DPCPX (8-Cyclopentyl-1,3-dipropylxanthine). Following a 30-min post-incubation period, cells were pelleted, layered with oil and ischemically incubated for 180 min. Injury was assessed by osmotic swelling and trypan blue exclusion of sequential samples, and determination of the areas beneath the mortality curves. Adenosine produced a broad concentration-protection curve which was displaced to the right by DPCPX. The curve for A1-selective agonist CCPA was biphasic, with an initial response below 1 nM and a second above 1 microM. DPCPX abolished the early response leaving a steep monophasic curve between 0.1 and 10 microM CCPA. The APNEA curve appeared moriophasic, the major slope occurring between 1-100 nM; DPCPX (1 microM) shifted the concentration-response curve approximately 30-fold and decreased the slope. Adenosine receptor agonist BNECA produced preconditioning characterized by a shallow monophasic concentration-protection curve with a maximal effect of 49% and an EC50 of approximately 5 nM; DPCPX shifted the BNECA concentration-protection relationship approximately 40-fold with only a modest increase in slope. Analysis of the data suggests that induction of preconditioning results from interaction of agonists with the A1 receptor and a second adenosine receptor having properties consistent with the A3 receptor. Adenosine, CCPA, APNEA, BNECA and DPCPX each appear to be selective for the A1 adenosine receptor subtype in isolated rabbit cardiomyocytes.

Adenosine↗
PubMed1995

Pharmacokinetics of moricizine in young patients.

Moricizine is a novel phenothiazine antiarrhythmic agent that depresses the activity of ectopic foci, has a low incidence of adverse effects relative to other agents, and is useful in treating pediatric atrial ectopic tachycardia. A study was conducted to determine the pharmacokinetics of moricizine in children after oral administration. Moricizine was isolated from frozen serum obtained from four male patients (ages 7, 8, 9, and 18 years) receiving the drug for supraventricular tachycardia and analyzed by high-performance liquid chromatography with ultraviolet detection according to an established protocol. Peak serum levels were between 400 and 2000 ng/mL. Elimination of moricizine did not follow simple single-compartment pharmacokinetics. In three patients we observed an increase or slower decline in blood level occurring after 4 hours. Because of the paroxysmal nature of the tachycardias, decreases in patient heart rate could not be correlated with moricizine blood level. These results suggest that the pediatric pharmacokinetics of moricizine excretion are complex and may differ from those seen in adults.

Administration, Oral↗
PubMed1995

Diastolic dysfunction is not related to changes in glycaemic control over 6 months in type 2 (non-insulin-dependent) diabetes mellitus. A cross-sectional study.

Diastolic dysfunction may be the earliest marker of a diabetes-induced heart muscle disease which leads to the progressive development of cardiac failure. Left ventricular diastolic function was indirectly assessed using pulsed wave Doppler ultrasound mitral-flow velocities in 20 normotensive patients with a new diagnosis of type 2 diabetes mellitus, normal cardiac function and no evidence of coronary artery disease and in 16 age-matched normal subjects. Peak velocities of early (E) and late (A) left ventricular filling were measured. The median (interquartile ranges) peak E/A ratio was significantly reduced in the diabetic group 0.96 (0.8-1.2) vs 1.2 (1.1-1.3), P < 0.01. Despite improvements in glycaemic control over 3 months, HbA1c 9.9% (7.6%-10.5%) to 7.4% (6.5%-7.9%), P < 0.001, maintained at 6 months, HbA1c 7.0% (6.4%-7.3%), there were no changes in the E/A ratio, 0.96 (0.83-1.15) and 0.95 (0.83-1.17), respectively. Furthermore, there was no correlation between percentage change in HbA1c and E/A ratio over 6 months. The results of this study suggest that in patients with type 2 diabetes mellitus and normal systolic function, diastolic function was impaired at diagnosis and was not affected by an improvement in the glycaemic control.

Blood Glucose↗
PubMed1995

Beta-adrenoceptor changes in mononuclear leukocytes during pregnancy.

Leukocyte beta 2-adrenoceptors mirror similar receptors in the uterus. This study examined changes in beta 2-adrenoceptors and in cAMP production during pregnancy using peripheral mononuclear leukocytes isolated from 17 pregnant women and 5 nonpregnant controls. beta 2-Adrenoceptor density was determined by 125I-pindolol binding. cAMP production under basal and stimulated (10 microM isoproterenol) conditions was determined by radioimmunoassay. Groups were compared by unpaired t test. There was a nonsignificant decrease in the density of beta-adrenoceptors during pregnancy. While basal cAMP production was unchanged during pregnancy, stimulated cAMP production was decreased (44% of control, P < 0.001; 95% CI 33%-56%). Stimulated cAMP production per receptor was lower in leukocytes from pregnant women and was not a constant relationship, but was increased markedly in leukocytes having fewer than 400 beta-adrenoceptor sites per cell. There are significant changes in the coupling of beta-adrenoceptors to cAMP production during pregnancy without changes in beta-receptor density, affinity, or basal cAMP production.

Adult↗
PubMed1994

Investigation of the influence of acetylsalicylic acid on the steady state of long-term therapy with theophylline in elderly male patients with normal renal function.

The risk inherent in the clinical control of patients with theophylline is widely recognized. Elderly patients may present an additional risk because of altered pharmacokinetics and the use of concomitant medication. Acetylsalicylic acid has been proposed for primary and secondary prevention of myocardial infarction and possible strokes. This investigation was undertaken to determine if concomitant administration of acetylsalicylic acid in elderly patients would alter steady-state levels of theophylline. A population of smoking male patients older than 60 years of age under long-term control of chronic obstructive pulmonary disease (COPD) with theophylline were evaluated for a baseline period of 3 days. Serum levels were measured at 6:00 AM and 6:00 PM. An enteric-coated acetylsalicylic acid preparation, 650 mg by mouth, was added to the daily slow-release theophylline, 6:00 AM hour dose regimen for 4 weeks. The serum levels of theophylline and salicylates were measured at 6:00 PM after dosing and at 6:00 AM the following day, at weekly intervals for 4 weeks. Urine specimens collected before administration of medication at 6:00 AM were analyzed for salicylates to further confirm dosage compliance. All volunteers continued to be clinically controlled throughout the treatment period and no symptoms of either overdose or underdose of either medication occurred. Plateau or trough theophylline serum levels did not change significantly during the salicylate treatment period. Salicylate serum levels did show during treatment self-induced metabolism. It is concluded that in elderly male patients, a daily concomitant therapeutic salicylate regimen does not alter steady-state serum theophylline levels and therefore does not per se necessitate the assay of theophylline blood levels in elderly patients.

Aged↗
PubMed1994

Insecticidal properties of several monoterpenoids to the house fly (Diptera: Muscidae), red flour beetle (Coleoptera: Tenebrionidae), and southern corn rootworm (Coleoptera: Chrysomelidae).

House flies, Musca domestica (L.), and their eggs were treated with 22 monoterpenoids to determine the topical, fumigant, and ovicidal activity of each compound. Fumigant activity of 14 monoterpenoids were examined further using red flour beetles, Tribolium castaneum (Herbst). Third-instar southern corn rootworm, Diabrotica undecimpunctata howardi Barber, were treated with carvacrol, citral, citronellal, menthol, pulegone, verbenol, and verbenone to determine their activity on larvae. Structure-activity relationships were evaluated with the toxicity data. We made comparisons between monocyclic aromatic, acyclic aliphatic, monocyclic aliphatic, and bicyclic aliphatic alcohols, ketones, aldehydes, and acids to determine toxicity differences involving the skeletal structure, amount of saturation, and associated functional groups of monoterapenoids. Ketones were more effective than alcohols in the topical, fumigant (T. castaneum), and ovicidal bioassays and less toxic than an analogous aldehyde in the topical, fumigant (M. domestica), and ovicidal bioassays. Aldehydes were more toxic than alcohols in the topical and fumigant (M. domestica) bioassays. In the topical and ovicidal bioassays, aromatic or acyclic alcohols, or both, were more effective than monocyclic and bicyclic alcohols. Vapors of bicyclic ketones were more toxic than monocyclic ketones to adult M. domestica. Monoterpenoid alcohols containing three carbon-carbon double bonds were more effective than saturated alcohols in the topical and larval bioassays. A mono-unsaturated ketone was more toxic than a structurally similar saturated ketone and two di-unsaturated ketones when it was applied topically to adult M. domestica. A saturated monocyclic ketone inhibited egg hatch more effectively than unsaturated monocyclic ketones.

Acyclic Monoterpenes↗
PubMed1993

The effect of short-term exercise on plasma procoagulant activity in patients with type II (non-insulin-dependent) diabetes and healthy volunteers.

The effect of exercise on plasma coagulant activity was studied in 16 subjects with newly-diagnosed type II diabetes without vascular complications and 9 healthy volunteers. Generation of thrombin was determined by a computer-assisted chromogenic method and results expressed as time to generate 50% maximal thrombin activity (T50/s). In addition, APTT, factor VIII and thrombin-antithrombin III (TAT) complex levels were measured. Pre-exercise FVIII:C [mean (+/- SD)] was increased in diabetic compared to control subjects [1.5 (0.4); 0.9 (0.2) IU ml-1; (p < 0.001) respectively]. No significant differences in APTT, TAT or T50 were detected between the groups. Exercise induced a rise in FVIII complex, reduction of APTT [33 (2) s to 31 (2) s; (p = 0.004)] and T50 [58 (6) s to 53 (6) s; (p = 0.01)] in controls and an increase in FVIII complex but no significant changes in APTT or T50 in diabetic patients, with no change in TAT in either group. A greater increase in FVIII:C than vWF levels occurred in controls [0.2 (0.1); 0.1 (0.1) IU ml-1; (p = 0.005)] and patients [0.3 (0.4); 0.2 (0.1) IU ml-1; (p = 0.032)]. In patients, FVIII:C correlated inversely with APTT (r = -0.522, p = 0.038) and T50 (r = -0.592, p = 0.016). The results show that FVIII:C levels are increased at diagnosis in patients with type II diabetes without vascular disease but there is no enhancement of plasma procoagulant activity. In healthy individuals, exercise induced activation of coagulation which was not seen in patients, suggesting that it does not precipitate a state of accelerated thrombogenesis in subjects with uncomplicated type II diabetes.

Blood Coagulation Factors↗
PubMed1992

The anatomical distribution of plasma fibrinolytic activity in man during cardiac catheterisation.

Regional circulating plasma levels of fibrinolytic activity were assessed in 15 patients undergoing cardiac catheterisation. The euglobulin clot lysis time (ECLT) was longer in the abdominal aorta (AA) than the inferior vena cava (IVC), (median difference -17.5 min, p = 0.008). This was associated with higher inhibition of plasminogen activator activity (PAI) in the AA than IVC, -1.75 IU/ml, p = 0.002. In the venous circulation the ECLT was higher in the peripheral venous sample than in the IVC, -25.5 min, p = 0.003, with higher PAI peripherally than in the IVC, -1.9 IU/ml, p = 0.001. There were no differences in ECLT, PAI, PAI-1:Ag or t-PA:Ag throughout the arterial circulation. These results demonstrate higher fibrinolytic activity with lower inhibitor activity in the venous compared to the arterial circulation. Within the venous circulation fibrinolytic activity is lower peripherally with increased inhibitor activity.

Aged↗